On April 4, 2022, Rachel Narehood Austin, Barnard’s Diana T. and P. Roy Vagelos Professor of Chemistry, Christina Vizcarra, assistant professor of chemistry, and several Barnard affiliates published new research in the journal Chemical Science. The article, titled “Metal Binding and Interdomain Thermodynamics of Mammalian Metallothionein-3: Enthalpically Favoured Cuᐩ Supplants Entropically Favoured Zn²ᐩ to form Cuᐩ4 Clusters Under Physiological Conditions,” was co-authored by Rahma Elsiesy ’20, Marina Orman ’11, and lab technician Rabina Lakha. Their work examines the binding of Zn²ᐩ and Cuᐩ to metallothioneins (MTs), a class of proteins involved in metal detoxification and homeostasis.
In order to enable condition-independent values for changes in entropy and enthalpy, the researchers measured Zn²ᐩ binding by chelation titrations of Zn7MT-3, and Cuᐩ binding by Zn²ᐩ displacement from Zn7MT-3 with the introduction of glutathione (GSH). Comparisons of the binding thermodynamics indicate that entropically-favored Zn²ᐩ is displaced by enthalpically-favored Cuᐩ, which forms Cuᐩ4-thioate clusters. These findings provide a greater understanding of the role that MT-3 plays in the chemistry of copper, and give an in-depth analysis of d¹⁰ metal binding to thiolate-rich proteins.